Tuesday, February 17, 2026 2/17/2026

Molecular regulation of fluid pressure homeostasis in the inner ear

Award Number: R01DC021710
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2029

Group Awards By:

View Award Description

Molecular regulation of fluid pressure homeostasis in the inner ear - Molecular regulation of fluid pressure homeostasis in the inner ear Project Summary A significant portion of hearing and balance disorders are caused by the unregulated accumulation of endolymph fluid and pressure within the inner ear. A key challenge in treating these diseases of elevated endolymph pressure is identifying new strategies to regain pressure homeostasis. We previously discovered a tissue-scale pressure relief valve in the epithelial tissue of the endolymphatic sac whose behavior is consistent with long observed physiologies that lacked explanations. Despite its importance in maintaining an internal environment within the ear, the molecular and cellular mechanisms by which the endolymphatic sac forms and functions remain unclear. The long-term goal of this research is to define how molecular signals during development and during homeostasis control the pressure relief valve's setpoint. Using a combination of advanced live imaging, genetics, and cell and molecular biological technologies like genome editing, we study these systemic processes in zebrafish embryos and larvae whose inner ears are optically accessible in the living animal instead of buried within the temporal bone as in mice and humans. Our prior generation of a single-cell gene expression atlas of the zebrafish inner ear identified molecular leads of signaling pathways in the endolymphatic sac. Synthesis with past work motivates our central hypothesis which posits that cells within the endolymphatic duct maintain a strong adhesive interaction, while adhesion strength at distinct subsets of cell-cell interfaces in the endolymphatic sac is reduced by adhesion protein turnover. This regulatory mechanism allows these interfaces to temporarily separate, facilitating the release of excessive pressure. We will pursue how the integration of molecular signals regulates these local cell behaviors to determine the pressure setpoint within the entire inner ear. First, we will determine how regulation of spatiotemporal differences in Wnt signaling regulate turnover rates of cell-cell adhesion complexes in subregions of the endolymphatic duct and sac. Second, we will determine the molecular responses in the endolymphatic sac that are regulated by vasopressin and how these responses integrate into physiological circuits. Third, we will determine how mechanical and calcium signals contribute to tissue contractions in the endolymphatic sac to regulate resistance to stretch. These studies will uncover regulatory mechanisms that determine the inner ear's pressure setpoint that are essential for our ability to sense sound for hearing and body acceleration for balance.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $524,996 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Research Related to Deafness and Communication Disorders	000	2	4/10/2025	NON-COMPETING CONTINUATION	$472,496
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Research Related to Deafness and Communication Disorders	001	2	4/21/2025	NON-COMPETING CONTINUATION	$52,500
														Subtotal = $524,996

Issue Date FY: 2024 ( Subtotal = $524,996 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Research Related to Deafness and Communication Disorders	000	1	3/5/2024	NEW	$524,996
														Subtotal = $524,996

Grand Total All Awards = $1,049,992

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Molecular regulation of fluid pressure homeostasis in the inner ear

Award Number: R01DC021710

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer